Featured Research

from universities, journals, and other organizations

Genome engineering system generates valuable conditional mouse models

Date:
August 29, 2013
Source:
Whitehead Institute for Biomedical Research
Summary:
The gene regulation system CRISPR/Cas (for “clustered regularly interspaced short palindromic repeat/CRISPR-associated) has been used to engineer mouse genomes containing reporter and conditional alleles in one step. Animals containing such sophisticated engineered alleles can now be made in a matter of weeks rather than years, and could be used to model diseases and study gene function.

Whitehead Institute researchers used CRISPR/Cas to engineer the genomes this mouse embryonic stem cell (ESC) to containing a reporter (V5) and a conditional allele (Sox2) in one step. Sox2 is a gene that is highly expressed in ESCs. The image on the left shows the expression of the Sox2-V5 allele (red) uniformly throughout the cell. In the middle image, the cell's DNA is stained blue. The right image was produced by merging the other two images together.
Credit: Cell Press

Whitehead Institute researchers have used the gene regulation system CRISPR/Cas to engineer mouse genomes containing reporter and conditional alleles in one step. Animals containing such sophisticated engineered alleles can now be made in a matter of weeks rather than years and could be used to model diseases and study gene function.

“We’ve used CRISPR/Cas to mutate genes before, but the nature of the targeted mutations has been unpredictable,” says Whitehead Founding Member Rudolf Jaenisch. “Now we can make specific deletions defined by two cuts. We can use this to make conditional mice in one step, and we can easily and very efficiently insert pieces of DNA up to three thousand base pairs It used to be much more work to make such mice.”

The CRISPR/Cas (for “clustered regularly interspaced short palindromic repeat/CRISPR-associated) system is based on an immune defense against viral invaders in bacteria and archaea. Scientists recently have adapted that defense to alter the genomes of mouse and human cells quickly and efficiently. Until now, however, researchers had yet to use CRISPR/Cas to create one of the most useful tools for genetic research: the conditional mutant mouse.

A conditional mutant mouse’s genome contains a gene or collection of genes that can be turned on or off using a particular signal. By turning the genes on or off, scientists can tease apart the role of certain genes in biological functions and diseases.
Previously, scientists created such model organisms using a complex and time-consuming process that requires using embryonic stem cells (ESCs). Unfortunately, scientists have only been able to efficiently manipulate the ESCs of mice and rats, a restriction that has hobbled this type of research.

Using CRISPR/Cas, Jaenisch and his lab have created mice with conditional alleles, as well as mice that carry multiple tagged genes that report whether these genes are being expressed. Their work is described in the September 12 issue of the journal Cell.

The researchers’ experiments also allay concerns regarding CRISPR/Cas’s off-target activity.

“Recent studies in human cancer cell lines raised some concerns on the specificity of CRISPR/Cas,” says Chikdu Shivalila, a co-author of the Cell paper and a graduate student in the Jaenisch lab, “Our study shows that the non-specific DNA cleavages could happen, but they are rare and predictable.”

The Jaenisch lab’s latest work opens up a number of avenues for future research.

“The methods we described in this work will greatly accelerate the speed of generating gene modified animals,” says Hui Yang, a postdoctoral researcher in the Jaenisch lab and co-author. “I’d like to use CRISPR/Cas to establish sophisticate disease models using this method.”

Because CRISPR/Cas does not rely on ESCs, it can be used to genetically modify any animal, including livestock.

“We haven’t tried it yet, but I’d like to adapt the CRISPR/Cas system for genome engineering in large animals, such as primate for disease modeling, or cattle for agricultural purposes,” says Haoyi Wang, a co-author and a postdoctoral researcher in the Jaenisch lab. “If so, this method could be very important economically, too.”


Story Source:

The above story is based on materials provided by Whitehead Institute for Biomedical Research. The original article was written by Nicole Giese Rura. Note: Materials may be edited for content and length.


Journal Reference:

  1. Hui Yang, Haoyi Wang, ChikduS. Shivalila, AlbertW. Cheng, Linyu Shi, Rudolf Jaenisch. One-Step Generation of Mice Carrying Reporter and Conditional Alleles by CRISPR/Cas-Mediated Genome Engineering. Cell, 2013; DOI: 10.1016/j.cell.2013.08.022

Cite This Page:

Whitehead Institute for Biomedical Research. "Genome engineering system generates valuable conditional mouse models." ScienceDaily. ScienceDaily, 29 August 2013. <www.sciencedaily.com/releases/2013/08/130829123448.htm>.
Whitehead Institute for Biomedical Research. (2013, August 29). Genome engineering system generates valuable conditional mouse models. ScienceDaily. Retrieved July 31, 2014 from www.sciencedaily.com/releases/2013/08/130829123448.htm
Whitehead Institute for Biomedical Research. "Genome engineering system generates valuable conditional mouse models." ScienceDaily. www.sciencedaily.com/releases/2013/08/130829123448.htm (accessed July 31, 2014).

Share This




More Health & Medicine News

Thursday, July 31, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Dangerous Bacteria Kills One in Florida

Dangerous Bacteria Kills One in Florida

AP (July 31, 2014) Sarasota County, Florida health officials have issued a warning against eating raw oysters and exposing open wounds to coastal and inland waters after a dangerous bacteria killed one person and made another sick. (July 31) Video provided by AP
Powered by NewsLook.com
Health Insurers' Profits Slide

Health Insurers' Profits Slide

Reuters - Business Video Online (July 30, 2014) Obamacare-related costs were said to be behind the profit plunge at Wellpoint and Humana, but Wellpoint sees the new exchanges boosting its earnings for the full year. Fred Katayama reports. Video provided by Reuters
Powered by NewsLook.com
Peace Corps Pulls Workers From W. Africa Over Ebola Fears

Peace Corps Pulls Workers From W. Africa Over Ebola Fears

Newsy (July 30, 2014) The Peace Corps is one of several U.S.-based organizations to pull workers out of West Africa because of the Ebola outbreak. Video provided by Newsy
Powered by NewsLook.com
Weather Kills 2K A Year, But Storms Aren't The Main Offender

Weather Kills 2K A Year, But Storms Aren't The Main Offender

Newsy (July 30, 2014) Health officials say 2,000 deaths occur each year in the U.S. due to weather, but it's excessive heat and cold that claim the most lives. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

    Environment News

    Technology News



      Save/Print:
      Share:

      Free Subscriptions


      Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

      Get Social & Mobile


      Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

      Have Feedback?


      Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
      Mobile: iPhone Android Web
      Follow: Facebook Twitter Google+
      Subscribe: RSS Feeds Email Newsletters
      Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins